This invention relates to biodegradable tissue scaffolds and drug delivery systems comprising porous and non-porous, regenerated cellulose (RC) and oxidized regenerated cellulose (ORC) membranes, and methods of using the same.
Organ or tissue failure is a major health crisis. Tissue engineering presents the potential to restore tissue function by using composites containing functional healthy cells from different sources (i.e. autogenic, allogeneic, or xenogeneic cells), and extracellular natural or synthetic polymers. Synthetic polymers must be biodegradable and biocompatible, be capable of fabrication into a porous three-dimensional membrane structure, and possess a range of physicochemical, mechanical, and degradative properties. The success of a promising polymer depends, in part, on the attachment and growth of the cells of interest on its surface. Thus, the surface chemistry, including hydrophobic/hydrophilic balance, mediates cellular response to the material and affects cell adhesion, proliferation, migration, and function on the surface.
A number of synthetic polymers, such as poly(glycolic acid), poly(lactic acid), poly(glycolide-co-lactide) copolymers, poly(xcex5-caprolactone), poly(dioxanone), and poly(glycolide-co-trimethylene carbonate) are currently being investigated as potential scaffolds for tissue engineering. Cellulose and its derivatives, such as cellulose acetates, have been extensively used as immobilizing matrices. However, these polymers are not biodegradable and, hence, are not suitable for use as implantable carrier systems.
Cellulose produced by microorganisms has been investigated for use as immobilizing matrices and implantable carriers. Microbial cellulose has a network structure in which very fine ribbon-shaped fibers composed of a highly crystalline and highly uniaxially oriented cellulose are complicatedly entangled with one another, and this network structure contains a large quantity of a liquid in interior voids thereof. Since the cellulose is composed of many ribbon-shaped fibers having a high crystallinity, the cellulose can resist external forces such as a tensile force even in the wet state. The microbial cellulose is not structurally different from a cellulose originating from a plant, but a high-order structure such as the above-mentioned structure is not found in the plant-originating cellulose although it is characteristic of the microbial cellulose. Accordingly, the microbial cellulose has a high strength though it is gelatinous.
Nevertheless, the use of microbial cellulose poses various problems compared with other widely used polymeric materials. More specifically, since thermoplastic polymeric materials represented by polyethylene and polyesters are made plastic by an application of heat or the addition of a softener, they can be molded into a desirable shape without changing their physical properties. Furthermore, these polymeric materials can be formed into any required shape or can be laminated by dissolution in a solvent or the like. In contrast, since microbial cellulose has the above-mentioned network structure without plasticity, if the microbial cellulose is dissolved in a solvent, the characteristics based on the characteristic high-order structure of the microbial cellulose are lost, and no substantial differences can be found between the microbial cellulose and the plant-originating cellulose. In addition, microbial celluloses must be treated to remove bacterial cultures prior to placement in the body.
Accordingly, it is a primary objective of the present invention to provide regenerated cellulose (RC) and oxidized regenerated cellulose (ORC) membranes as drug delivery systems and tissue scaffolds and methods of using the same.
It is a further objective of the present invention to provide RC and ORC membranes as drug delivery systems and tissue scaffolds that are biodegradable and biocompatible.
It is yet a further objective of the present invention to provide porous RC and ORC membranes as drug delivery systems and tissue scaffolds that have highly interconnected pore networks.
It is a further objective of the present invention to provide RC and ORC membranes as tissue scaffolds that are transparent and flexible.
It is still a further objective of the present invention to provide RC and ORC membranes as drug delivery systems and tissue scaffolds that provide attachment sites for drugs, proteins, and cells.
It is a further objective of the present invention to provide RC and ORC membranes as drug delivery systems and tissue scaffolds that are derived from a natural, non-microbial source.
It is a further objective of the present invention to provide RC and ORC membranes with good mechanical strength.
It is still a further objective of the present invention to provide RC and ORC membranes that may be modified to biodegrade at a particular rate.
The method and means of accomplishing each of the above objectives as well as others will become apparent from the detailed description of the invention which follows hereafter.
The present invention describes the preparation of regenerated celluloses (RC) and oxidized regenerated celluloses (ORC) as biodegradable drug delivery systems and tissue scaffolds. The RC and ORC composites are produced by first dissolving cellulose in a solvent system, then regenerating the cellulose into a desired scaffold structure. To produce porous scaffolds, a porogen is introduced in the solvent system to produce pores in the scaffold structure. The scaffold may then be oxidized to introduce carboxyl, aldehyde, and/or ketone functional groups on its surface. These functional groups serve as sites for cell attachment or further chemical modification to induce cell adhesion and subsequent proliferation.
The RC and ORC scaffolds produced in accordance with this invention are biodegradable and biocompatible, and therefore are suitable for implanting in the body. They may be used in a wide variety of biological and medical applications, including drug delivery, promotion of tissue and bone growth, as artificial blood vessels, as a substitute for human skin, dental implants, and micronerve surgery.